Project Summary The prevalence of cigarette smoking among people living with HIV (PLWH) in the US is about double that among the general population. Tobacco and HIV may act synergistically to increase morbidity and mortality risks. Among PLWH on antiretroviral therapy (ART), smoking now reduces life expectancy more than HIV itself. The footprint of smoking will likely grow as PLWH age. Compared to the general population, PLWH have been less likely to quit smoking. Smoking cessation interventions have not been widely implemented in HIV care, partly due to the lack of guidance for patients and care providers on the optimum cessation strategies in this population. While improvements in HIV care have largely been focused on novel antiretroviral drug regimens, there is still much to be accomplished in reducing the burden of smoking-attributable disease. In an environment of growing attention to resource utilization, where annual ART costs exceed $30,000 per patient, evaluating the cost-effectiveness of smoking cessation interventions in promoting abstinence and reducing the toll of smoking is critically important. I am a pulmonologist with a background in economics and prior experience in HIV and tuberculosis research. I am motivated to investigate efficient ways to reduce the burden of disease caused by smoking and HIV. Simulation modeling can project long-term clinical and economic outcomes of behaviors, diseases, and interventions. My long-term goal is to become a world expert on the application of evidence- and model-based approaches to clinical decision-making and public health policy at the intersection of tobacco, HIV, and lung disease. In my recent research training, I have learned the fundamentals of disease simulation via a validated and widely-published computer simulation of HIV natural history and outcomes, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-US model. To achieve independence, I require further training in: 1) modeling complex health behaviors; 2) deriving clinical and economic outcome data; and 3) designing and conducting cost-effectiveness analysis. To enhance my methodologic skills in these areas, I have outlined a plan of didactic coursework and assembled a multidisciplinary mentorship team. My primary mentor is Dr. Rochelle Walensky, an expert in HIV outcomes research and modeling, and my co-mentor is Dr. Nancy Rigotti, an international authority in tobacco cessation interventions and control policy. My mentorship team additionally includes experts in behavioral science (Park), comorbidities in PLWH (Triant), lung disease epidemiology (Christiani), chronic obstructive pulmonary disease in PLWH (Medoff), applied epidemiology and biostatistics (Parker), resource utilization and health economics (Resch), mathematical modeling and cost-effectiveness analysis (Weinstein and Paltiel), and HIV outcomes and policy (Freedberg). With their guidance, I will leverage the CEPAC-US model to achieve the following specific research aims: 1) to expand a pilot US tobacco/HIV simulation model to account for changes in an individual's smoking behaviors over time; 2) to determine the clinical and economic impacts ? including those related to myocardial infarction, chronic obstructive pulmonary disease, and lung cancer ? of smoking among PLWH; and 3) to examine the cost-effectiveness of interventions, including behavioral counseling and pharmacotherapy, to reduce smoking-associated morbidity and mortality among PLWH. This research responds directly to the 2016 priority areas of the NIH Office of AIDS Research, which considers HIV-associated comorbidities to be a high priority topic. The research plan is innovative by integrating HIV with smoking behaviors, outcomes, and costs. Cost-effectiveness analysis can help clinicians and policymakers prioritize among interventions for PLWH. Massachusetts General Hospital, Harvard Medical School, and Harvard T.H. Chan School of Public Health provide an exceptional intellectual and collaborative environment for this research. Building on my prior research experience and training, the existing CEPAC-US model, and methodologic training via coursework and expert mentorship, I am well-positioned to accomplish the proposed aims and ultimately apply for an R01 award focused on tobacco use and HIV disease.